Authors: Farokh R Demehri Susanne M Krug Yongjia Feng InFah M Lee Joerg D Schulzke Daniel H Teitelbaum
Publish Date: 2015/12/21
Volume: 61, Issue: 6, Pages: 1524-1533
Abstract
Total parenteral nutrition TPN a necessary treatment for patients who cannot receive enteral nutrition is associated with infectious complications due in part to a loss of intestinal epithelial barrier function EBF Using a mouse model of TPN with enteral nutrient deprivation we previously demonstrated an increase in mucosal interferonγ and tumor necrosis factorα these cytokine changes are a major mediator driving a reduction in epithelial tight junction TJ protein expression However the exact ultrastructural changes to the intestinal epithelial barrier have not been previously describedC57BL/6 mice underwent internal jugular venous cannulation and were given enteral nutrition or TPN with enteral nutrient deprivation for 7 days Freezefracture electron microscopy was performed on ileal tissue to characterize changes in TJ ultrastructure EBF was measured using transepithelial resistance and tracer permeability while TJ expression was measured via Western immunoblotting and immunofluorescence stainingWhile strand density linearity and appearance were unchanged TPN dependence led to a mean reduction in one horizontal strand out of the TJ compact meshwork to a more basal region resulting in a reduction in meshwork depth These findings were correlated with the loss of TJ localization of claudin4 and tricellulin reduced expression of claudin5 and claudin8 and reduced ex vivo EBF
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